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      Comparative Efficacy of Feline Leukemia Virus (FeLV) Inactivated Whole-Virus Vaccine and Canarypox Virus-Vectored Vaccine during Virulent FeLV Challenge and Immunosuppression

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          Abstract

          Four vaccines for feline leukemia virus (FeLV) are available in the United States. This study's purpose was to compare the efficacy of Nobivac feline 2-FeLV (an inactivated, adjuvanted whole-virus vaccine) and PureVax recombinant FeLV (a live, canarypox virus-vectored vaccine) following FeLV challenge. Cats were vaccinated at 9 and 12 weeks with Nobivac feline 2-FeLV (group A, n = 11) or PureVax recombinant FeLV (group B, n = 10). Group C ( n = 11) comprised unvaccinated controls. At 3 months postvaccination, cats were immunosuppressed and challenged with FeLV-A/61E. The outcomes measured were persistent antigenemia at 12 weeks postchallenge (PC) and proviral DNA and viral RNA at 3 to 9 weeks PC. Persistent antigenemia was observed in 0 of 11 cats in group A, 5 of 10 cats in group B, and 10 of 11 cats in group C. Group A was significantly protected compared to those in groups B ( P < 0.013) and C ( P < 0.0001). No difference was found between groups B and C ( P > 0.063). The preventable fraction was 100% for group A and 45% for group B. At 9 weeks PC, proviral DNA and viral RNA were detected 1 of 11 cats in group A, 6 of 10 cats in group B, and 9 of 11 cats in group C. Nucleic acid loads were significantly lower in group A than in group C ( P < 0.01). Group A had significantly lower proviral DNA loads than group B at weeks 6 to 9 ( P < 0.02). The viral RNA loads were significantly lower in group A than in group B at weeks 7 to 9 ( P < 0.01). The results demonstrate that Nobivac feline 2-FeLV-vaccinated cats were fully protected against persistent antigenemia and had significantly smaller amounts of proviral DNA and plasma viral RNA loads than PureVax recombinant FeLV-vaccinated cats and unvaccinated controls.

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          Most cited references20

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          2008 American Association of Feline Practitioners' feline retrovirus management guidelines.

          Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are among the most common infectious diseases of cats. Although vaccines are available for both viruses, identification and segregation of infected cats form the cornerstone for preventing new infections. Guidelines in this report have been developed for diagnosis, prevention, treatment, and management of FeLV and FIV infections. All cats should be tested for FeLV and FIV infections at appropriate intervals based on individual risk assessments. This includes testing at the time of acquisition, following exposure to an infected cat or a cat of unknown infection status, prior to vaccination against FeLV or FIV, prior to entering group housing, and when cats become sick. No test is 100% accurate at all times under all conditions; results should be interpreted along with the patient's health and risk factors. Retroviral tests can diagnose only infection, not clinical disease, and cats infected with FeLV or FIV may live for many years. A decision for euthanasia should never be based solely on whether or not the cat is infected. Vaccination against FeLV is highly recommended in kittens. In adult cats, antiretroviral vaccines are considered non-core and should be administered only if a risk assessment indicates they are appropriate. Few large controlled studies have been performed using antiviral or immunomodulating drugs for the treatment of naturally infected cats. More research is needed to identify best practices to improve long-term outcomes following retroviral infections in cats.
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            Quantitation of feline leukaemia virus viral and proviral loads by TaqMan real-time polymerase chain reaction.

            Feline leukaemia virus (FeLV) infection in cats is not only of veterinary importance but also a well-acknowledged animal model for studying the pathogenesis of retroviral disease. After virus exposure, different courses and outcomes of FeLV infection may prevail; they have been associated with cellular and humoral immune responses and the FeLV proviral load in peripheral blood. We hypothesized that the plasma viral RNA load might be an additional relevant indicator for the infection outcome. To quantify these loads, a real-time reverse transcriptase (RT) polymerase chain reaction (PCR) assay was developed. The assay amplifies FeLV-A, -B, and -C as some naturally infected cats could not be identified with a FeLV-A-based assay previously. The assay was applied to determine plasma FeLV RNA loads in cats infected both naturally and experimentally with FeLV. In addition, an improved real-time PCR assay for quantitation of FeLV proviral loads is described. The assays developed were more sensitive than ELISA and virus isolation in the early phase of infection. In addition, PCR allows the identification of provirus carriers that have overcome antigenaemia. Thus, for most effective detection of FeLV exposure and characterization of the infection in a cat, PCR assays are recommended as diagnostic tools.
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              Feline leukaemia provirus load during the course of experimental infection and in naturally infected cats.

              Feline leukaemia virus (FeLV) infection in domestic cats can vary in its outcome (persistent, transient, no infection) for reasons that are not entirely known. It was hypothesized that the initial virus and provirus load could significantly influence the course of retrovirus infection. To determine the role of provirus loads, two methods of PCR, a nested PCR and a fluorogenic probe-based (TaqMan) real-time quantitative PCR, which were specific to the U3 region of FeLV-A were established. FeLV provirus in naturally and experimentally infected cats was then measured. Only 3 weeks after experimental FeLV-A infection, persistently infected cats demonstrated higher provirus loads and lower humoral immune responses than cats that had overcome antigenaemia. Lower initial provirus loads were associated with successful humoral immune responses. Unexpectedly, provirus in the buffy-coat cells of two cats that tested negative for the p27 antigen (a marker for viraemia) was also detected. In 597 Swiss cats, comparison of p27 antigen levels with PCR results revealed broad agreement. However, similar to the experimental situation, a significant number of animals (10%) was negative for the p27 antigen and FeLV-positive by PCR. These cats had a mean provirus load 300-fold lower than that of animals testing positive for the p27 antigen. In conclusion, an association between the provirus load and the outcome of FeLV infection was found. Detection of provirus carriers should contribute to further the control of FeLV. In addition, quantification of provirus loads will lead to a better understanding of FeLV pathogenesis and anti-retrovirus protective mechanisms.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                Clin Vaccine Immunol
                Clin. Vaccine Immunol
                cdli
                cvi
                CVI
                Clinical and Vaccine Immunology : CVI
                American Society for Microbiology (1752 N St., N.W., Washington, DC )
                1556-6811
                1556-679X
                13 May 2015
                July 2015
                13 May 2015
                : 22
                : 7
                : 798-805
                Affiliations
                [a ]Merck Animal Health, Elkhorn, Nebraska, USA
                [b ]Merck Animal Health, Madison, New Jersey, USA
                Author notes
                Address correspondence to M. Bourgeois, melissa.bourgeois@ 123456merck.com .

                Citation Patel M, Carritt K, Lane J, Jayappa H, Stahl M, Bourgeois M. 2015. Comparative efficacy of feline leukemia virus (FeLV) inactivated whole-virus vaccine and canarypox virus-vectored vaccine during virulent FeLV challenge and immunosuppression. Clin Vaccine Immunol 22:798–805. doi: 10.1128/CVI.00034-15.

                Article
                00034-15
                10.1128/CVI.00034-15
                4478526
                25972402
                86638aa8-4678-4a00-ade0-dfd75c29bf7c
                Copyright © 2015, Patel et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 23 January 2015
                : 20 February 2015
                : 22 April 2015
                Page count
                Figures: 5, Tables: 1, Equations: 0, References: 26, Pages: 8, Words: 7497
                Categories
                Vaccines

                Immunology
                Immunology

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